Multiple sclerosis (MS) is an autoimmune disease where myelin is incorrectly recognized as foreign and attacked by the adaptive immune system. Dendritic cells (DCs) direct adaptive immunity by presenting antigens to T cells, therefore serving as a target for autoimmune therapies. N-Phenyl-7-(hydroxyimino) cyclopropa[b]chromen-1a-carboxamide (PHCCC), a positive allosteric modulator of metabotropic glutamate receptor 4 (mGluR4), can promote regulatory T cells by altering cytokine secretion to bias T cell differentiation. The therapeutic potential of PHCCC, however, is hindered by dose-limiting toxicity, poor solubility, and the need for frequent dosing. We hypothesized liposomal delivery of PHCCC might enable safe, effective delivery of this hydrophobic drug to exploit metabolism as a means of controlling inflammation in self-reactive immune cells. PHCCC was readily encapsulated in liposomes modified with polyethylene glycol. Under sink conditions, controlled release resulted in 58% of drug released into media over 18 hours. Culture of primary DCs with PHCCC liposomes reduced pro-inflammatory cytokine secretion while reducing toxicity four-fold compared with soluble PHCCC. During co-culture of DCs with myelin-reactive T cells from transgenic mice, PHCCC liposomes reduced T cell proliferation and interferon gamma secretion. These results support the potential of using liposomes to promote tolerance through biocompatible delivery of metabolic modulators. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2977-2985, 2017.

译文

多发性硬化症 (MS) 是一种自身免疫性疾病,其中髓磷脂被错误地识别为外来物质并受到适应性免疫系统的攻击。树突状细胞 (dc) 通过向T细胞呈递抗原来指导适应性免疫,因此可作为自身免疫疗法的靶标。N-Phenyl-7-(羟基亚氨基) 环丙 [b]chromen-1a-carboxamide (PHCCC) 是代谢型谷氨酸受体4 (mGluR4) 的正变构调节剂,可以通过改变细胞因子分泌来促进调节性T细胞分化。然而,PHCCC的治疗潜力受到剂量限制毒性,溶解度差以及需要频繁给药的阻碍。我们假设PHCCC的脂质体递送可能使这种疏水药物的安全,有效的递送能够利用代谢作为控制自我反应免疫细胞中炎症的手段。PHCCC很容易封装在用聚乙二醇修饰的脂质体中。在下沉条件下,受控释放导致药物在18小时内释放到培养基中的58%。与可溶性PHCCC相比,用PHCCC脂质体培养原代dc可减少促炎性细胞因子的分泌,同时降低毒性的四倍。在dc与转基因小鼠的髓磷脂反应性T细胞共培养期间,PHCCC脂质体降低了T细胞的增殖和干扰素 γ 的分泌。这些结果支持了使用脂质体通过代谢调节剂的生物相容性递送来促进耐受性的潜力。©2017威利期刊公司J生物材料Res部分A: 105A: 2977-2985,2017。

+1
+2
100研值 100研值 ¥99课程
检索文献一次
下载文献一次

去下载>

成功解锁2个技能,为你点赞

《SCI写作十大必备语法》
解决你的SCI语法难题!

技能熟练度+1

视频课《玩转文献检索》
让你成为检索达人!

恭喜完成新手挑战

手机微信扫一扫,添加好友领取

免费领《Endnote文献管理工具+教程》

微信扫码, 免费领取

手机登录

获取验证码
登录